COFACTOR REQUIREMENT FOR CD4-MEDIATED HIV-1 ENTRY

CD4 介导的 HIV-1 进入的辅助因子要求

• 批准号: 2057610
• 负责人: Robert D. Harrington
• 金额: $ 8.09万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2057610
• 关键词: HeLa cells; clone cells; cofactor; genetic library; helper T lymphocyte; human immunodeficiency virus 1; life cycle; transfection; virus infection mechanism; virus replication

Research. Expression of the HIV-I receptor CD4 on many non-human and see human cell lines is not sufficient to permit HIV-I infection. The investigator describes human glioblastoma cell line (U373) which remains resistant to HIV-1 despite the added expression of an authentic CD4 molecule. The block to H1V- 1 infection of these cells is strain- independent and appears to be at viral entry. Heterokaryons of CD4- expressing U373 (U373-CD4) cells fused to HeLa cells allow HIV-I entry. A U373-CD4\HeLa hybrid clone allows efficient HIV-I replication. These results suggest that HeLa cells express a factor(s) that can complement the viral entry defect of U373-CD4 cells and which is necessary for efficient HIV-l infection. Experiments that test the ability of additional human cell lines to complement U373-CD4 cells will provide insight into the complexity of the viral entry process. Studies to identify the chromosome encoding the complementing gene and the gene itself will help define the cellular requirements for CD4-mediated HIV-l infection and may provide new targets for interrupting the viral life cycle.

Research. HIV-1受体CD 4在许多非人类和非人类的细胞上的表达， 人类细胞系不足以允许HIV-I感染。 的 研究者描述了人胶质母细胞瘤细胞系（U373）， 抗HIV-1，尽管增加了真正的CD 4 分子。这些细胞对H1 V- 1感染的阻断是应变- 独立的，似乎是在病毒进入。CD 4-的异核体 与HeLa细胞融合的表达U373（U373-CD 4）细胞允许HIV-1进入。一 U373-CD4\HeLa杂交克隆允许有效的HIV-I复制。这些 结果表明，HeLa细胞表达一种因子， U373-CD 4细胞的病毒进入缺陷，这是有效的 HIV-1感染测试额外人类细胞能力的实验 补充U373-CD 4细胞的细胞系将提供对复杂性的深入了解， 病毒进入的过程研究以确定编码 互补基因和基因本身将有助于定义细胞 CD 4介导的HIV-1感染的需要，并可能提供新的靶点 来中断病毒的生命周期